16-11927438-ATGG-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BS1 BS2

The NM_001396485.1(NPIPB2):c.1126_1128del(p.Pro376del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00919 in 142,928 control chromosomes in the GnomAD database, including 13 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0092 (13 hom., cov: 31)
  • Exomes 𝑓: 0.0033 (29 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPB2 NM_001396485.1 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0890

Genes affected

NPIPB2 (HGNC:37451): (nuclear pore complex interacting protein family member B2) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001396485.1
• BP6: Variant 16-11927438-ATGG-A is Benign according to our data. Variant chr16-11927438-ATGG-A is described in ClinVar as [Likely_benign]. Clinvar id is 2646232.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00919 (1313/142928) while in subpopulation SAS AF= 0.0235 (110/4690). AF 95% confidence interval is 0.0199. There are 13 homozygotes in gnomad4. There are 665 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPIPB2	NM_001396485.1	c.1126_1128del	p.Pro376del	inframe_deletion	8/8	ENST00000399147.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPIPB2	ENST00000399147.8	c.1126_1128del	p.Pro376del	inframe_deletion	8/8	5	NM_001396485.1
NPIPB2	ENST00000547494.6	c.1075_1077del	p.Pro359del	inframe_deletion	8/8	5		P1
NPIPB2	ENST00000673243.1	c.706_708del	p.Pro236del	inframe_deletion	10/10
NPIPB2	ENST00000698171.1	c.1024_1026del	p.Pro342del	inframe_deletion	7/7

Frequencies

GnomAD3 genomes AF: 0.00914 AC: 1305 AN: 142840 Hom.: 13 Cov.: 31

Gnomad AFR AF: 0.00391

Gnomad AMI AF: 0.00221

Gnomad AMR AF: 0.0108

Gnomad ASJ AF: 0.0122

Gnomad EAS AF: 0.000392

Gnomad SAS AF: 0.0232

Gnomad FIN AF: 0.00528

Gnomad MID AF: 0.00980

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.00656

GnomAD3 exomes AF: 0.00298 AC: 442 AN: 148460 Hom.: 5 AF XY: 0.00274 AC XY: 218 AN XY: 79692

Gnomad AFR exome AF: 0.00119

Gnomad AMR exome AF: 0.00192

Gnomad ASJ exome AF: 0.00192

Gnomad EAS exome AF: 0.0000898

Gnomad SAS exome AF: 0.00511

Gnomad FIN exome AF: 0.00136

Gnomad NFE exome AF: 0.00368

Gnomad OTH exome AF: 0.00406

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00334 AC: 3573 AN: 1071148 Hom.: 29 AF XY: 0.00367 AC XY: 1986 AN XY: 541762

Gnomad4 AFR exome AF: 0.00120

Gnomad4 AMR exome AF: 0.00233

Gnomad4 ASJ exome AF: 0.00572

Gnomad4 EAS exome AF: 0.000116

Gnomad4 SAS exome AF: 0.00821

Gnomad4 FIN exome AF: 0.00704

Gnomad4 NFE exome AF: 0.00284

Gnomad4 OTH exome AF: 0.00387

GnomAD4 genome AF: 0.00919 AC: 1313 AN: 142928 Hom.: 13 Cov.: 31 AF XY: 0.00951 AC XY: 665 AN XY: 69910

Gnomad4 AFR AF: 0.00407

Gnomad4 AMR AF: 0.0108

Gnomad4 ASJ AF: 0.0122

Gnomad4 EAS AF: 0.000393

Gnomad4 SAS AF: 0.0235

Gnomad4 FIN AF: 0.00528

Gnomad4 NFE AF: 0.0117

Gnomad4 OTH AF: 0.00699

Alfa AF: 0.0141 Hom.: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

NPIPB2: BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs60347225; hg19: chr16-12021295;